The antibiotic daptomycin is produced by the Gram-positive bacterium Streptomyces roseosporus and is the first in a new class of investigational drugs called lipopeptides that is being developed by Cubist for the treatment of serious and life-threatening infections caused by Gram-positive pathogens. The goal of this phase I application is to develop a system that will allow the rapid manipulation of the daptomycin biosynthetic gene cluster. These tools would then be used in phase II of the application to elucidate the structure activity realtionships (SAR) of daptomycin and use this information to create derivatives of daptomycin with increased potency against vancomycin resistant pathogens. [unreadable] [unreadable]